| Insulin resistance(IR) is important factor and dominant feature in type 2 diabetes mellitus pathogenesis.Therefore IR treatment is the most important in prevention and treating diabetes mellitus and metabolic syndrome.Chinese medicine mainly apply compound recipe to treat disease,displaying features of integral regulation and combined therapy.Chinese herbal compound effective material basis are its chemical compositions or active sites,however just a few monomer compounds cannot be representing the whole recipe,should attach more important to the role of of chemical constituents group or active sites.Active sites effective application compatibility,there maybe present synergy,while reducing theextent of adverse reactions.Therefore,under the guidance of TCM theory,compatibility apply Chinese medicine active sites to develop innovative drugs,set up innovative Chinese medicine studying mode with demonstration effects,to improve the overall quality and competitiveness of Chinese medicine industry.Huang QI San ancient recipe origin from《Shengji Zonglu》,composed by radix Pueraria,Radix Astragali,Cortex Mori.rhe three medicines compatible application,could be nourishing qi to invigorate spleen,benefiting vital energy and clean fever,nourishing qi to invigorate spleen,treating triple diabetes together,to play the role of treating appearance and substance together.Much research indicate that the three medicines have the good curative effect to T2DM or IR,which active material and mechanism of effect are all different,therefore the recipe is presumed be through multi-ways, and multi-target targets comprehensive effect improve T2DM-IR.At present, the study based on Huang Qi San has not been reported,so its clinical application and development has certain limitation.The research firstly based on the whole recipe,attempted to interpret the effect and mechanism of Huang Qi San intervention in T2DM-IR,then apply a series of modern Chinese medicine purification and pharmaceutical production technology,to gather each medicine active sites,to make foundation for further preparations development.Partâ… :Literature reviewAll recent relevant literature concerning T2DM-IR modern medicine research progression,concerning epidemiology,etiopathogenisis,and pathogenesis studies are documented.We also review the literature concerning TCM recognition in DM,chemical composition and Huang Qi San each medicine pharmacology research progression.So this study made a systematic review of mechanism,pathogenesis and allopathic medicine studies of IR in T2DM into consideration both TCM and modern medicine,latest molecule pathogenesis study achievement,and animal model establish and experiments study,to prehensile related advancing front research developments.Partâ…¡:Laboratory studies1.The studies on effects and mechanisms of Huang Qi San interfere in laboratory IR in type 2 diabetes.To assess the effects of Huang Qi San on streptozocin(STZ) inducing DM mouse model,Hydrocortisone Sodium Succinate(HSCC) inducing IR mouse model. The results showed that Hang Qi San can lower fasting blood sugar(FBG) and increase sugar tolerance,and increase insulin sensibility of mice with abnormal sugar tolerance but not DM,to improve insulin resistance.Use STZ with high fat diet to set up T2DM-IR rat model.We determine model rat FBG,fasting insulin(FINS),sugar tolerance,insulin tolerance,insulin sensitivity index(ISI),and insulin resistance index(HOMA-IR),lipid metabolism and free fatty acids content of serum and hepatic,HE staining of pancreas,to observe the effects of Huang Qi San on glycolipid metabolism and insulin resistance in T2DM-IR.The results showed Huang Qi San can significant lower FBG,improve sugar tolerance,lower serum hyperinsulinism induced by IR,increase insulin tolerance,ISI,lower HOMA-IR index,and protect pancreatic tissue structure.Meanwhile,Huang Qi San can regulate blood fat, hepatic lipid,down regulate serum and hepatic FFA level.That indicate Huang Qi San can improve glycolipid metabolism,increase insulin sensitivity to cure IR.On the basis of T2DM-IR model rats,apply radioimmunity(RI) method to determine TNF-α,leptin content in serum,apply RT-PCR method and immunohistochemical method to observe mRNA and protein expression of GLUT-4, IRS-lin liver,skeletal muscle and adipose tissue,apply RT-PCR method determine adipose tissue PPAR-γmRNA expression,to illuminate the mechanisms of Huang Qi San improve IR.The results showed the mechanisms of Huang Qi San improving IR followed as:â‘ Up-regulate T2DM-IR rats skeletal muscle and adipose tissue GLUT-4 mRNA and protein expression,increase liver, skeletal muscle and adipose tissue IRS-1mRNA and protein expression,to regulate insulin signal transduction,promot glucose transportation,increase periphery tissue insulin sensitivity.â‘¡Down-regulate significantly TNF-α, leptin content in serum,improve organism leptin sensitivity,to improve organism insulin sensitivity.â‘¢Promote adipose tissue PPAR-γmRNA expressions,which are important receptor for controlling insulin sensitivity, improve indirectly IR.2.The Preparation of Basic Research on Huang Qi SanExamine quality of radix puerariae and radix astragali from different habitats,to sieve mediocre quality medical material for technology study. Studies were carried on the extraction and purification process of total flavonoids by comparing total flavonoids extract yield and purity of the impact of ethanol concentration,ratio of herb to solvent,extraction time,extraction times and extraction temperature.Set up the L9(34) orthogonal test and confirmed the best extraction process as 10BV 70%ethanol distilling two times, 2h per time.Extract of total flavonoids was purified with macroeticular resins. Different kinds of resins were applied to inspect the static and dynamic adsorption ability,to optimize the concentration,volume and flow rate of eluant.It was confirmed that the best purification process was AB-8 macroeticular resins,medical material dried resins being 2:1,sample fluid concentration being 0.10g dried medicinal herb per milliliter,eluted in order by 10BV distilled water,10BV 50%ethanol with flow rate of 1～3ml/min.50% ethanol part was collected,dried under vacuum and freeze drying resulting in the total flavonoids purity above 62.0%.Total flavonoids extract were prepared by 10 lots radix puerariae.The studies established TLC method. confirmed the limits of loss on drying,established quantitative analysis method of total flavonoids by ultra-voilet spectrophotometry and puerarin by RP-HPLC,for establishing the criteria of quality control of radix puerariae total flavonoids extract.Studies were carried on the extraction and purification process of radix astragali total saponins by comparing total saponins extract yield and purity of the impact of ethanol concentration,ratio of herb to solvent,extraction time,extraction times and extraction temperature.Set up the L9(34) orthogonal test and confirmed the best extraction process as 8BV 70%ethanol distilling three times,1.5h per time.Extract of total saponins was purified with macroeticular resins.Different kinds of resins were applied to inspect the static and dynamic adsorption ability,to optimize the concentration,volume and flow rate of ehant.It was confirmed that the best purification process was AB-8 macroeticular resins,medical material dried resins being 3:1,sample fluid concentration being 0.075g dried medicinal herb per milliliter,eluted in order by 10BV distilled water,10BV 0.5%NaOH,10BV 10%ethanol,10BV 70% ethanol with flow rate of 1～3ml/min.70%ethanol part was collected,dried under vacuum and freeze drying resulting in the total saponins purity above 68.0%.Total saponins extract were prepared by 10 lots radix astragali.The studies established TLC method,confirmed the limits of loss on drying, established quantitative analysis method of total saponins by ultra-voilet spectrophotometry and astragalosideâ…£by RP-HPLC-ELSD for establishing the criteria of quality control of radix astragali total saponins extract.
|
PDF Full Text Request